A substance P antagonist increases brain intracellular free magnesium concentration after diffuse traumatic brain injury in rats

J Am Coll Nutr. 2004 Oct;23(5):538S-540S. doi: 10.1080/07315724.2004.10719398.


Objective: Magnesium (Mg) deficiency has been shown to increase substance P release and induce a pro-inflammatory response that can be attenuated with the administration of a substance P-antagonist. Neurogenic inflammation has also been implicated in traumatic brain injury (TBI), a condition where brain intracellular free magnesium (Mg(f)) decline is known to occur and has been correlated with functional outcome. We therefore examined whether a substance P antagonist restores brain intracellular free magnesium concentration following TBI.

Methods: Male, adult Sprague-Dawley rats were injured using the Cernak impact acceleration model of diffuse TBI. At 30 min after injury, animals were administered either 0.25 mg/kg i.v. n-acetyl tryptophan or equal volume saline. Prior to and 4 h after induction of injury, phosphorus magnetic resonance spectra were acquired using a 7-tesla magnet interfaced with a Bruker console. Mg(f) was calculated from the chemical shift of the beta ATP. Before injury, Mg(f) was 0.51 +/- 0.05 mM (SEM).

Results: By 4 hr after injury, Mg(f) had significantly declined to 0.27 +/- 0.02 mM in saline treated rats. In contrast, rats treated with n-acetyl tryptophan had a Mg(f) of 0.47 +/- 0.06 mM at 4 h after injury, which was not significantly different from preinjury values. There were no significant differences in pH between the treatment groups.

Conclusion: It seems that any beneficial effect of a substance P antagonist on functional outcome following TBI may be related to improvement in brain Mg homeostasis induced by the compound.

MeSH terms

  • Animals
  • Brain Injuries / metabolism*
  • Homeostasis
  • Magnesium / metabolism*
  • Magnesium Deficiency
  • Magnetic Resonance Spectroscopy
  • Male
  • Protease Inhibitors / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Substance P / antagonists & inhibitors*
  • Tryptophan / analogs & derivatives*
  • Tryptophan / pharmacology*


  • Protease Inhibitors
  • Substance P
  • N-acetyltryptophan
  • Tryptophan
  • Magnesium